Table 1

Clinical characteristics and outcomes of 3 patients with S. aureus endocarditis treated with a combination of high-dose daptomycin and fosfomycin

Parameter(s)Patient 1Patient 2aPatient 3
Age (yr)545371
Chronic underlying diseasesScleroderma, severe pulmonary artery hypertension, elective aortic and mitral double-valve replacement with mechanical prostheses 11 yr ago, MRSEc prosthetic-valve endocarditis 10 years ago needing an aortic valve homograftDiabetes mellitus, HIV-HBVb coinfectionDiabetes mellitus, diabetic foot infection, Child-Pugh class B liver cirrhosis, mild mitral regurgitation due to severe valve calcification
Drug allergiesPenicillin, vancomycinNoneNone
Source of infectionUnknownLeft inguinal infection by MRSA 2 weeks after lymph node biopsyMRSA-infected foot ulcer
Clinical characteristicsHigh-grade fever, cerebral and splenic emboli, coma, additive EuroSCOREe of 18High-grade fever, malaise, pain in neck and index finger of left handHigh-grade fever, splenic emboli
Blood cultures before treatment6/6 positive for MSSA6/6 positive for MRSA6/6 positive for MRSA
Antibiotic susceptibilities (MIC, μg/ml)Vancomycin, 1; fosfomycin, 8; daptomycin, 1Vancomycin, 1.5; fosfomycin, ≤ 32; daptomycin, 1Vancomycin, 1.5; fosfomycin, ≤ 32; daptomycin, 1
TEEd findings1-cm aortic homograft valve vegetation, 10 by 8 mm perivalvular abscess, no prosthetic valve dysfunctionCalcification of aortic and mitral valves, no evidence of vegetations or perivalvular abscessesMitral valve rupture with severe regurgitation, 1-cm mitral valve vegetation, 6 by 8 mm perivalvular abscess
Initial i.v. antibiotic therapy (no. of days)Daptomycin at 10 mg/kg/day (7)Daptomycin at 4 mg/kg/day (2), daptomycin at 4 mg/kg/day plus gentamicin at 240 mg/48 h (5), daptomycin at 8 mg/kg/day plus gentamicin at 240 mg/48 h (3)Vancomycin at 15 mg/kg every 12 h; vancomycin trough plasma concentrations, 11 and 20 μg/ml on days 2 and 5, respectively
Complications of first-line treatmentNoneProgressive renal failure; need for hemodialysis; signs of septic embolization along left sternal margin and on first left metacarpal joint, second and third right toes, right forefoot, and left sternocleidomastoid muscle at day 2; pyomyositis with compression of oropharynx at day 10Serum creatinine increase from 1.4 to 3.0 mg/dl (normal, ≤1.3 mg/dl) during first 24 h but return to normal level after 2 days
Follow-up blood cultures after initial treatmentPositive at days 3, 7Positive at days 3, 7, 10Positive at day 5
No. of days from initial treatment to switch to daptomycin plus fosfomycin7105
Doses given i.v. (daptomycin, fosfomycin)10 mg/kg/day, 2 g/6 h10 mg/kg/day, 2 g/6 h10 mg/kg/day, 2 g/6 h
Time of first negative blood cultures after switch to daptomycin plus fosfomycin (h)724848
Duration of treatment (wk)866
Complications of daptomycin plus fosfomycin treatmentNoneTransmetatarsal amputation of right foot, chronic hemodialysisNone
Follow-up blood cultures after daptomycin plus fosfomycinNegative at days 14, 42Negative at days 14, 28, 42, 90Negative at days 30, 90
Clinical follow-upAlive at 1 yrAlive at 1 yrAlive at 6 mo
  • a Patient 2 could be considered to have possible endocarditis according to the Duke criteria.

  • b HBV, hepatitis B virus.

  • c MRSE, methicillin-resistant S. epidermidis.

  • d TEE, transesophageal echocardiography.

  • e See references 7 and 16.